Final Diagnosis -- Intracranial xanthogranuloma

DIAGNOSIS

Intracranial xanthogranuloma.

DISCUSSION

Proliferative histiocytic conditions are defined as a heterogenous group of tumor-like lesions that share an abnormal accumulation of cells of the mononuclear phagocytic system, which are either dendritic cell type or macrophage type. They include a wide range of conditions that occur in children and adults. These disorders have been difficult to classify and to treat. Various different classifications are available (12, 13). The histiocytic lesions have been divided into 3 broad categories: 1. the common Langerhans cell histiocytosis which includes histiocytosis X (eosinophilic granuloma) and Hand-Schüller-Christian disease; 2. the less common, Non-Langerhans cell histiocytosis which includes xanthogranuloma, Erdheim-Chester disease, hemophagocytic lymphohistiocytosis & Rosai-Dorfman disease and; 3.the malignant histiocytosis which include histiocytic sarcoma, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma and follicular dendritic cell sarcoma. Xanthogranulomas are benign dendritic cell non-Langerhans histiocytic proliferations which preferentially affect the skin of the head, neck and trunk of mainly young children. However, 15% to 30% of these lesions have also been reported in older individuals (11). Clinically xanthogranulomas are classified into a) cutaneous forms; b) cutaneous forms with systemic involvement and; c) xanthogranulomas that are associated with syndromes (13). The organs involved in the systemic type usually include eye, lung, epicardium, oral cavity, testis and soft tissue. The eye is the most common extra cutaneous site (11). The central nervous system is a very unusual site for xanthogranulomas. Intracranial xanthogranulomas are asymptomatic in the majority of cases and discovered only at autopsy (5). Most of them arise in the choroid plexus of the ventricular systems (14). Lesions have also been reported in Meckel's cave, pineal region, cerebellopontine angle, the sciatic nerve, and the orbital region (1, 2, 6, 7, 9). Dura based symptomatic xanthogranulomas are particularly rare (3).

Dural xanthogranulomas have been associated with histiocytosis X, familial hyperlipoproteinemia, Weber-Christian disease and Erdheim-Chester disease (8). Our patient did not fit into any syndrome. She is a known case of diabetes insipidus, so the possibility of Erdheim-Chester disease was considered. Erdheim-Chester disease is a rare systemic disease with a non-Langerhans cell histiocytic proliferation of the viscera and bones that is clinically characterized by bone pain, diabetes insipidus, and exophthalmos. Skeletal radiographs of long bones, full body computed tomography and magnetic resonance imaging of the whole spine failed to demonstrate bony osteosclerotic lesions characteristic to this disease. No other mass lesion was identified. In addition other features like bone pain, retroperitoneal fibrosis and exophthalmos were absent.

The pathogenesis of xanthogranuloma remains a matter of debate. A majority of the xanthogranulomas appear to originate from a common precursor CD34 progenitor hematopoietic stem cell (12,13). It is yet to be determined whether this condition is neoplastic, inflammatory or metabolic. An alternate pathogenesis describes the development of xanthogranuloma secondary to trauma (10). In our patient there is no history of trauma.

The histological differential diagnoses of intracranial dura based xanthogranuloma include various histiocytic disorders (e.g. Langerhans cell histiocytosis), primary central nervous system tumors with xanthomatous change (e.g. meningioma, epithelioid schwannoma, pleomorphic xanthoastrocytoma, capillary hemangioblastoma), tumor-like conditions (e.g. inflammatory pseudotumor, cholesterol granuloma, tuberculoma) and non-neoplastic reactive processes or inflammatory condition associated with increased number of macrophages (e.g. infection and demyelinating disorders). Distinction from Langerhans cell histiocytosis was straight forward. The histiocytes in our case were foamy unlike the convoluted histiocytes of Langerhans cell histiocytosis. There were fewer eosinophils. Touton giant cells which were numerous in our case are typically rare in Langerhans cell histiocytosis. Features like CD1a positivity on immunohistochemistry and presence of Birbeck granules on electron microscopy characteristic to Langerhans cells were also absent. Inflammatory pseudotumor (plasma cell granuloma) can also present as a meningeal based intracranial space occupying lesion. Inflammatory pseudotumors have a rich lymphohistiocytic and plasma cell infiltrate. They also comprise a significant SMA and ALK-1 positive, myofibroblastic spindle cell population. Our case was negative with SMA and ALK-1. Histologically cholesterol granulomas and xanthogranulomas are quite similar, but there were no cholesterol clefts and hemosiderin laden macrophages in our case. The histiocytes of tuberculoma are more epithelial in appearance, and are commonly associated with Langhans type giant cells and abundant necrosis. These features were missing in the current case. In addition, Ziehl-Neelsen stain for acid fast bacilli was negative. Various primary central nervous tumors can mimic xanthogranulomas and were excluded based on morphology and immunohistochemical stain such as EMA (positive in meningioma), GFAP (positive in pleomorphic xanthoastrocytoma), S100 (positive in epithelioid schwannoma) and CD34 (positive in capillary hemangioblastoma). All the previously mentioned stains were negative in our case. As for the non-neoplastic reactive processes, they usually do not present as space occupying lesions and have variable radiological and clinical manifestations.

Conventional craniotomy with complete resection is adequate treatment for such lesions. Adjuvant therapy in form of radiotherapy or chemotherapy may be necessary for multicentric or non-resectable lesions (4).

In conclusion, a symptomatic large frontoparietal subdural intracranial xanthogranuloma is extremely rare, especially in the absence of associated systemic disease. There are no characteristic radiological features for the diagnosis of intracranial xanthogranulomas and therefore, histopathology plays an essential role in definitive diagnosis. Our patient remains asymptomatic and the follow-up radiology did not reveal an increase in the size of the residual lesion.